ABSTRACT— Information on the ultrastructure and phenotypes of proliferative hepatocytes is scarce, so we set out to detect proliferating hepatocytes immunohistochemically by use of a monoclonal antibody against DNA polymerase alpha (DNA-PA). The findings from this method were compared with conventional features, such as mitotic figures, and hepatic regeneration after injury was considered in the light of these findings. The subjects of the basic study were 23 patients with acute hepatic failure. There were 6.8 ± 5.5 (mean ± SD) mitotic hepatocytes per 1000 hepatocytic nuclei, and 209 ± 158 hepatocytes stained for DNA-PA per 1000 hepatocytic nuclei. By light and electron microscopy (n=4), hepatocytes stained for DNA-PA showed various morphological features, including development of organelles, but some resembled hepatocytes in mitosis. Accordingly, this histochemical method may be useful in studies of hepatic regeneration. In acute confluent necrosis, when hepatocytic proliferation is urgently needed for survival, small hepatocytes next to necrotic areas (probably immature cells, to judge from the development of their organelles) were predominant in hepatic regeneration. These findings suggest that hepatocytes in different stages of development can easily enter the mitotic cell cycle repeatedly when rapid regeneration is needed.